A new model of persistent viral infection with primary demyelination

Abstract

Theiler's encephalomyelitis virus (TMEV) in mice represents one of the few existing animal models of virus-induced demyelination and may provide further information about the human disease, Multiple Sclerosis. An inbred strain of mice (SJL/j) employed in the present ultrastructural study, develops a life-long neurologic illness characterized by profound spasticity after intracerebral inoculation of TMEV. Anesthetized animals were sacrificed sequentially by total body perfusion with gluteraldehyde from 7 days to 9 months after infection. An intense mononuclear inflammatory infiltrate appeared in the leptomeninges and white matter of spinal cord by 15 days and persisted for as long as one year. These infiltrates contained numerous plasma cells, and perivascular demyelination could be found in almost every 1 micron section. Vesiculation and stripping of myelin by mononuclear cell processes were seen as mechanisms of myelin break-down. However, virions were not found in cells in grey or white matter and the integrity of oligodendrocytes was maintained. At one year, active demyelination was still seen in areas containing naked and remyelinated axons. The relevance of these ultrastructural findings to postulated mechanisms of virus-induced demyelination will be discussed.